Sokhna Keita-Alassane1, Colombe Otis1,2, Emilie Bouet1, Martin Guillot1,3, Marilyn Frezier1, Aliénor Delsart1, Maxim Moreau1,2, Agathe Bédard3, Isabelle Gaumond4, Jean-Pierre Pelletier2, Johanne Martel-Pelletier2, Francis Beaudry1,2, Bertrand Lussier1,2, Roger Lecomte5,6, Serge Marchand4,6, Eric Troncy7,8. 1. Research Group in Animal Pharmacology of Quebec (GREPAQ), Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, Université de Montréal, Saint Hyacinthe, QC, Canada. 2. Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC, Canada. 3. Charles River Laboratories Montreal ULC, Senneville, QC, Canada. 4. Département de Chirurgie, Département d'anesthésie, Faculté de Médecine Et Des Sciences de La Santé, Université de Sherbrooke, Sherbrooke, QC, Canada. 5. Sherbrooke Molecular Imaging Center, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. 6. Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Sherbrooke, QC, Canada. 7. Research Group in Animal Pharmacology of Quebec (GREPAQ), Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, Université de Montréal, Saint Hyacinthe, QC, Canada. eric.troncy@umontreal.ca. 8. Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC, Canada. eric.troncy@umontreal.ca.
Abstract
PURPOSE: Several observational studies suggest that estrogens could bias pain perception. To evaluate the influence of estrogenic impregnation on pain expression, a prospective, randomized, controlled, blinded study was conducted in a Sprague-Dawley rat model of surgically induced osteoarthritis (OA). METHODS: Female rats were ovariectomized and pre-emptive 17β-estradiol (0.025 mg, 90-day release time) or placebo pellets were installed subcutaneously during the OVX procedures. Thirty-five days after, OA was surgically induced on both 17β-estradiol (OA-E) and placebo (OA-P) groups. Mechanical hypersensitivity was assessed by static weight-bearing (SWB) and paw withdrawal threshold (PWT) tests. Mass spectrometry coupled with high-performance liquid chromatography (HPLC-MS) was performed to quantify the spinal pronociceptive neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), somatostatin (SST), and dynorphin-A (Dyn-A). RESULTS: Compared to control, ovariectomized rats presented higher SP (P = 0.009) and CGRP (P = 0.017) concentrations. OA induction increased the spinal level of SP (+ 33%, P < 0.020) and decreased the release of BK (- 20%, (P < 0.037)). The OA-E rats at functional assessment put more % body weight on the affected hind limb than OA-P rats at D7 (P = 0.027) and D56 (P = 0.033), and showed higher PWT at D56 (P = 0.009), suggesting an analgesic and anti-allodynic effect of 17β-estradiol. Interestingly, the 17β-estradiol treatment counteracted the increase of spinal concentration of Dyn-A (P < 0.016) and CGRP (P < 0.018). CONCLUSION: These results clearly indicate that 17β-estradiol interfers with the development of central sensitization and confirm that gender dimorphism should be considered when looking at pain evaluation.
PURPOSE: Several observational studies suggest that estrogens could bias pain perception. To evaluate the influence of estrogenic impregnation on pain expression, a prospective, randomized, controlled, blinded study was conducted in a Sprague-Dawley rat model of surgically induced osteoarthritis (OA). METHODS: Female rats were ovariectomized and pre-emptive 17β-estradiol (0.025 mg, 90-day release time) or placebo pellets were installed subcutaneously during the OVX procedures. Thirty-five days after, OA was surgically induced on both 17β-estradiol (OA-E) and placebo (OA-P) groups. Mechanical hypersensitivity was assessed by static weight-bearing (SWB) and paw withdrawal threshold (PWT) tests. Mass spectrometry coupled with high-performance liquid chromatography (HPLC-MS) was performed to quantify the spinal pronociceptive neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), somatostatin (SST), and dynorphin-A (Dyn-A). RESULTS: Compared to control, ovariectomized rats presented higher SP (P = 0.009) and CGRP (P = 0.017) concentrations. OA induction increased the spinal level of SP (+ 33%, P < 0.020) and decreased the release of BK (- 20%, (P < 0.037)). The OA-E rats at functional assessment put more % body weight on the affected hind limb than OA-P rats at D7 (P = 0.027) and D56 (P = 0.033), and showed higher PWT at D56 (P = 0.009), suggesting an analgesic and anti-allodynic effect of 17β-estradiol. Interestingly, the 17β-estradiol treatment counteracted the increase of spinal concentration of Dyn-A (P < 0.016) and CGRP (P < 0.018). CONCLUSION: These results clearly indicate that 17β-estradiol interfers with the development of central sensitization and confirm that gender dimorphism should be considered when looking at pain evaluation.